Typical examples of microorganisms which are known as antigen to cause certain appreciable cell-mediated immune response in living animals and humans include tubercle bacillus belonging to bacteria and vaccinia virus belonging to viruses. Notice has recently been taken of tubercle bacillus with great interest since BCG vaccine and a cell-wall substance of tubercle bacillus were found to exhibit an immunological antitumor action. However, no extensive use of such antigenic bacteria and the cell materials thereof in clinical applications has yet been made due to side effects associated with them. Attention was once taken about the antitumor action of vaccinia virus. However, the inoculation of an animal body with vaccinia virus generally leads to establishment of a substantial humoral immunity in the living animal body, which, in turn, results in no substantial enhancement of the antitumor effect. For this reason, no great attention has been paid to vaccinia virus in these days.
We have extensively studied in search of an attenuated strain of vaccinia virus which may exhibit a reduced humoral immune activity and an enhanced cellular (cell-mediated) immune activity. As a result, we have now found that when vaccinia virus, either directly or after the serial passages thereof in mouse kidney cell monolayer culture, is serially passed in chick embryo cell monolayer culture, then the virus has been attenuated to such an extent that it has no substantial pock-forming capacity in rabbits but that the attenuated virus possesses both a humoral immune activity reduced to a substantial degree preferably down to substantial naught and a considerably enhanced cell-mediated immune activity in mice, as compared with the original virus. The attenuated strain of vaccinia virus thus obtained has been found to be effective as cellular immunopotentiator and immune antitumor agent.